Ovarian cancer is the second most common gynecologic cancer in US women, but often diagnosed at a late stage, it is the leading cause of gynecologic cancer mortality in 2008. In the absence of effective and widespread ovarian cancer screening, identifying a new risk factor for ovarian cancer, which is assessed through another cancer screening tool---mammography-could be of considerable value to the field. The majority of US adult women report having at least one mammogram. In addition to detecting breast cancer, mammograms allow assessment of mammographic breast density. Mammographic breast density is one of the strongest risk factors for breast cancer-a 3-6-fold increased risk of breast cancer in women with denser breasts compared to women with less dense breasts. Mammographic breast density is believed to be a marker for cumulative estrogen exposure. However, breast density has not yet been evaluated as a risk factor for ovarian cancer, even though it has a shared hormonal etiology with breast cancer.7, 8 Mammographic breast density-if related to ovarian cancer-would be a clinically feasible and efficient way of identifying women potentially at high-risk for ovarian cancer. The specific aims of this project are: 1) to estimate the association between mammographic breast density and incident ovarian cancer risk among women aged 40-79 years who participated in the Breast Cancer Surveillance Consortium during 1996-2008; and 2) to determine if the association between mammographic breast density and incident ovarian cancer risk is modified by ovarian cancer risk factors, including parity, hormone therapy use, oral contraceptive use, family history of breast or ovarian cancer, and menopausal status. We propose to investigate these aims in a cohort of women participating in the Breast Cancer Surveillance Consortium (BCSC), a national multi-site cohort of US women and mammography in community practice. To date, the BCSC has accumulated more than 8.6 million mammograms from over 2.2 million women and diagnosed more than 100,000 breast cancers. We expect to ascertain over 3,200 cases of incident ovarian cancer during 1996-2008, and an average of 8 years of follow-up. Breast density was assessed by the radiologist at the time of mammography according to BI-RADS(R) density scale: Category 1, almost entirely fatty; Category 2, scattered fibroglandular densities; Category 3, heterogeneously dense; and Category 4, extremely dense. We will use Cox proportional hazards modeling to estimate adjusted hazard ratios of ovarian cancer associated with breast density category. We will evaluate effect modification by ovarian cancer risk factors, and test for interaction with likelihood ratio test. The novelty of this application lies in the potential ability to improve screening for ovarian cancer through a short, low-impact, and low-cost intervention-breast density from mammography screening. There is the potential that mammography could be used not only to inform our clinical understanding of breast cancer, but could also be informative for ovarian cancer. PUBLIC HEALTH RELEVANCE: The purpose of this project is to determine whether breast density judged at mammography increases or decreases the risk of ovarian cancer among women in the Breast Cancer Surveillance Consortium. We will also look at whether certain groups of women are more likely to get ovarian cancer than other women. This is important research because there are few new risk factors for ovarian cancer, and we might identify a risk factor that is also measured at mammography, which would be important to many US women.